Movie of the ribosome's elongation cycle, in which a growing peptide chain is elongated by addition of one amino acid, is based in part on cryo-electron microscopy studies of ribosome-ligand complexes. The ribosome (with P-site tRNA in green) is shown rotating and then stationary, with its large subunit on top and its small subunit on bottom. The ribosome surface is peeled away to reveal the intersubunit space and a P-site tRNA. mRNA is added as a string of colored beads, where each set of three beads represents a codon. A tRNA with an amino acid (bead) arrives as part of a complex with elongation factor Tu (red). The growing peptide on the P-site tRNA is elongated by peptide transfer. The tRNAs then move together with mRNA by one codon to the adjacent sites, a process called translocation, which is catalyzed by EF-G (gray).

The Royal Swedish Academy of Sciences has awarded the 2009 Nobel Prize in Chemistry to three scientists “for studies of the structure and function of the ribosome,” the protein-making factory of cells. Ada E. Yonath, 70, of Weizmann Institute of Science, in Rehovot, Israel; Thomas A. Steitz, 69, of Yale University; and Venkatraman Ramakrishnan, 57, of the MRC Laboratory of Molecular Biology, in Cambridge, England, will share equally the $1.4 million prize. They all used X-ray crystallography to map the ribosome’s structure and study its complex mechanism of action.

“What an exciting day for those of us working on the ribosome,” says ribosome specialist Rachel Green of Johns Hopkins University School of Medicine. The prize “raises public awareness about the central role of the ribosome in all life processes, its overarching complexity, and the need for more research,” adds Joachim Frank of Columbia University, who studies the ribosome by cryoelectron microscopy.

The ribosome is a huge protein-RNA complex that is essential to life. The bacterial ribosome is the site of action for many antibiotics and continues to be a key target for antibiotic drug design.

The ribosome is composed of two subunits, small and large. In the small subunit, transfer RNAs (tRNAs) recognize protein-encoding information on messenger RNA (mRNA) transcribed from the genetic code. The large subunit includes the ribosome’s active site, where proteins are actually assembled by one-at-a-time addition of amino acids.

“The Nobel Prize committee had a substantial problem to solve because many people contributed” to unraveling the structure and function of the ribosome, says chemistry professor Peter B. Moore of Yale, who also studies the ribosome’s structure. “In my opinion, they really did their homework, and given that they could only pick three”—the limit for sharing a single prize—“they got the right three.”

“There was never any question that if a Nobel Prize were given for the ribosome, Yonath would be part of it,” Moore says. In 1980, Yonath and her coworkers, including the late biochemist H. G. Wittmann of Max Planck Institute for Molecular Genetics, in Berlin, obtained, after about 25,000 attempts, the first ribosome crystals, a prerequisite for crystallographic analysis. “At the time, no one had ever crystallized anything so complicated, so it was a remarkable achievement,” Moore says. Yonath and coworkers later carried out ribosome structure determinations as well.

In 2000, Steitz, Moore, and coworkers solved the first structure of the large subunit, and Yonath and Ramakrishnan obtained the first structures of the small subunit. “Those are the progenitors of all the structures of ribosomes that are out there today,” Moore says, including the first structure of the entire ribosome, obtained in 2001 by a group including Harry F. Noller of the University of California, Santa Cruz; Jamie H. D. Cate of UC Berkeley; and Marat Yusupov of the University of Strasbourg, in France. Steitz, Moore, and Noller later cofounded New Haven, Conn.-based Rib-X Pharmaceuticals, which uses ribosome structure data to design antibiotics.

Analyzing the ribosome “seemed to us a bit like trying to climb Mount Everest,” Steitz says. “But we found the right way, and when we got to the top in 2000, it was very exhilarating—the most exhilarating moment I’ve had in science—to peer into the inner workings of the ribosome and think about how it works.”